Dual gate biologically sensitive field effect transistor

ABSTRACT

A biologically sensitive field effect transistor includes a substrate, a first control gate and a second control gate. The substrate has a first side and a second side opposite to the first side, a source region and a drain region. The first control gate is disposed on the first side of the substrate. The second control gate is disposed on the second side of the substrate. The second control gate includes a sensing film disposed on the second side of the substrate. A voltage biasing between the source region and the second control gate is smaller than a threshold voltage of the second control gate.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. patent application Ser. No.14/961,588, filed on Dec. 7, 2015, which is incorporated herein byreference in its entirety.

BACKGROUND

Biosensors are devices for sensing and detecting biomolecules andoperate on the basis of electronic, electrochemical, optical andmechanical detection principles. Biosensors that include transistors aresensors that electrically sense charges, photons, and mechanicalproperties of bio-entities or biomolecules. The sensor detects theconcentration of bio-entities or biomolecules, or through interactionand reaction between specified reactants and bio-entities/biomolecules.Such biosensors are fast in signal conversion and can be manufacturedusing semiconductor processes and easily applied to integrated circuitsand MEMS.

A field effect transistor (FET) includes a source, a drain and a gateand may be used as a sensor for various types of targets. A biologicallysensitive field effect transistor, or bio-organic field effecttransistor, (Bio-FET) is created to detect biomolecules, including, forexample, H+, Ca2+, DNA, proteins and glucose. An electrolyte containingthe molecule of interest is used as the Bio-FET gate.

BRIEF DESCRIPTION OF THE DRAWINGS

Aspects of the present disclosure are best understood from the followingdetailed description when read with the accompanying figures. It isnoted that, in accordance with the standard practice in the industry,various features are not drawn to scale. In fact, the dimensions of thevarious features may be arbitrarily increased or reduced for clarity ofdiscussion.

FIG. 1 is a schematic cross-sectional diagram showing a dual gatebiologically sensitive field effect transistor (Bio-FET) in accordancewith some embodiments of the instant disclosure;

FIG. 2A is a schematic cross-sectional diagram showing a dual gatebiologically sensitive field effect transistor (Bio-FET) in accordancewith some embodiments of the instant disclosure;

FIG. 2B is a schematic diagram showing a simplified circuit route of adual gate biologically sensitive field effect transistor (Bio-FET) inaccordance with some embodiments of the instant disclosure;

FIG. 2C is a schematic diagram showing a simplified circuit layout of adual gate biologically sensitive field effect transistor (Bio-FET) inaccordance with some embodiments of the instant disclosure;

FIG. 3A is a graph showing current sensitivity to pH variation of a dualgate biologically sensitive field effect transistor (Bio-FET) inaccordance with some embodiments of the instant disclosure;

FIG. 3B is a graph showing pH sensitivity and transconductance of backgate in a dual gate biologically sensitive field effect transistor(Bio-FET) in accordance with some embodiments of the instant disclosure;

FIG. 4 is a graph showing current drift rate at various pH value of adual gate biologically sensitive field effect transistor (Bio-FET) inaccordance with some embodiments of the instant disclosure;

FIG. 5 is a schematic diagram showing a simplified circuit layout of adual gate biologically sensitive field effect transistor (Bio-FET) inaccordance with some embodiments of the instant disclosure;

FIG. 6 is a schematic diagram showing a simplified circuit layout of aseries of dual gate biologically sensitive field effect transistors(Bio-FET) in accordance with some embodiments of the instant disclosure;

FIG. 7A is a schematic diagram showing a detailed analogue circuitlayout of a dual gate biologically sensitive field effect transistor(Bio-FET) in accordance with some embodiments of the instant disclosure;

FIG. 7B is a schematic diagram showing a detailed digital circuit layoutof a dual gate biologically sensitive field effect transistor (Bio-FET)in accordance with some embodiments of the instant disclosure; and

FIG. 8 is a flow chart showing a method of threshold mismatchcalibration for sensory array in accordance with some embodiments of theinstant disclosure.

DETAILED DESCRIPTION

The following disclosure provides many different embodiments, orexamples, for implementing different features of the provided subjectmatter. Specific examples of components and arrangements are describedbelow to simplify the present disclosure. These are, of course, merelyexamples and are not intended to be limiting. For example, the formationof a first feature over or on a second feature in the description thatfollows may include embodiments in which the first and second featuresare formed in direct contact, and may also include embodiments in whichadditional features may be formed between the first and second features,such that the first and second features may not be in direct contact. Inaddition, the present disclosure may repeat reference numerals and/orletters in the various examples. This repetition is for the purpose ofsimplicity and clarity and does not in itself dictate a relationshipbetween the various embodiments and/or configurations discussed.

Further, spatially relative terms, such as “beneath,” “below,” “lower,”“above,” “upper” and the like, may be used herein for ease ofdescription to describe one element or feature's relationship to anotherelement(s) or feature(s) as illustrated in the figures. The spatiallyrelative terms are intended to encompass different orientations of thedevice in use or operation in addition to the orientation depicted inthe figures. The apparatus may be otherwise oriented (rotated 90 degreesor at other orientations) and the spatially relative descriptors usedherein may likewise be interpreted accordingly.

In a biologically sensitive field effect transistor (BioFET), the gateof a metal-oxide-semiconductor field-effect transistor (MOSFET) isreplaced by a bio- or biochemical-compatible layer or abiofunctionalized layer of immobilized probe molecules that act assurface receptors. A BioFET is primarily a field-effect biosensor with asemiconductor transducer, and the gate controls the conductance of thesemiconductor between its source and drain contacts.

Typical detection mechanism of BioFETs is the conductance modulation ofthe transducer resulting from the binding of a target biomolecule to thegate or to a receptor molecule immobilized on the gate. When the targetbiomolecule binds to the gate or the immobilized receptor, the draincurrent of the BioFET is changed by the gate potential. This fluctuationin the drain current can be measured, and the bonding between thereceptor and the target biomolecule can be identified. A great varietyof biomolecules may be used as the gate of the BioFET such as ions,enzymes, antibodies, ligands, receptors, peptides, oligonucleotides,cells of organs, organisms and pieces of tissue. For example, to detectsingle-stranded deoxyribonucleic acid (ssDNA), the gate of the BioFET isequipped with immobilized complementary ssDNA strands. Also, to detectvarious proteins such as tumour markers, monoclonal antibodies may beimplemented as the gate of the BioFET.

When an electric field is applied across a piece of material, theelectrons respond by moving with an average velocity called driftvelocity. This phenomenon is known as electron mobility. ConventionalBioFET sensors suffer from large accumulative drift effect. The drifteffect results from electrical field enhanced ion migration within thegate insulator, and the electrochemical non-equilibrium occurs at theinsulator-solution interface. In one example, the drift rate is as highas 36 nA/min under operation mode. The high drift rate may lead tocompromising in the sensitivity of the sensor. Many approaches have beenused to attenuate drift effect. For example, when a BioFET requirescalibration, a test power source is applied to the background, and acurrent change related to pH value in the solution is detected. Athreshold slope (current/time) is measured according to the currentchange. The signal then undergoes analogue/digital conversion in a CPU,and time drift data is extracted and stored in the memory. This timedrift data is used in the calibration when an analyte test is conducted.However, to obtain background time drift data is relatively timeconsuming, and the collective time drift data results in accumulativedeviation. Furthermore, the process requires complex hardware set, forexample, the analogue-digital converter, CPU and memory unit.

Another example of conventional BioFET calibration uses a reference FET(REFET) along with the existing BioFET. In contrast to the BioFET, thisREFET is non-biologically sensitive. REFET obtains the backgroundvoltage of the pH value in the solution along with time, while theBio-FET obtains the bio-sensitive voltage data alone with time. Adifferential measurement is then conducted between this pair. In thiscalibration system, REFET has to be fabricated in additional process,and once the drift effect in the REFET is taken into account, the errorrange may increase.

Still another example of conventional BioFET calibration system usespulse-modulated biasing to repeatedly reset vertical electrical fieldand therefore reduce the drift effect. In this approach, ahigh-frequency alternating current (AC) biasing is required. As aresult, a time discrete sample readout interface has to be designed forinterpreting the data.

Please refer to FIG. 1. FIG. 1 shows a dual gate BioFET sensor 100 inaccordance with some embodiments of the instant disclosure. The sensor100 includes a substrate 110, a first control gate 120 and a secondcontrol gate 130. It should be understood the number of the first andsecond control gates is not limited to one. The same system can beapplied to multiple control gate structure. For the sake of clarity,only a pair of first and second control gates is shown in the figures.The substrate 110 has a first side 111 and a second side 113 opposite tothe first side. The substrate 110 may be a semiconductor substrate(e.g., wafer). The semiconductor substrate may be a silicon substrate.Alternatively, the substrate 110 may include another elementarysemiconductor, such as germanium; a compound semiconductor includingsilicon carbide, gallium arsenic, gallium phosphide, indium phosphide,indium arsenide, and/or indium antimonide; an alloy semiconductorincluding SiGe, GaAsP, AlInAs, AlGaAs, GaInAs, GaInP, and/or GaInAsP; orcombinations thereof. In an embodiment, the substrate 110 is asemiconductor on insulator (SOI) substrate. The substrate may includedoped regions, such as p-wells and n-wells.

The source, drain, and/or channel region 115, 117, 119 are formed on anactive region of the substrate 110. The FET may be an n-type FET (nFET)or a p-type FET (pFET). For example, the source/drain regions 115, 117may include n-type dopants or p-type dopants depending on the FETconfiguration. The first control gate 120 is disposed on the first side111 of the substrate 110 and includes a gate dielectric layer 121, aninterconnect layer 123, a first gate electrode 125, and/or othersuitable layers. In an embodiment, the gate electrode 125 ispolysilicon. Other exemplary gate electrodes include metal gateelectrodes including material such as, Cu, W, Ti, Ta, Cr, Pt, Ag, Au;suitable metallic compounds like TiN, TaN, NiSi, CoSi; combinationsthereof and/or other suitable conductive materials. In an embodiment,the gate dielectric layer 121 is silicon oxide. Other exemplary gatedielectric layer 121 includes silicon nitride, silicon oxynitride, adielectric with a high dielectric constant (high k), and/or combinationsthereof. Examples of high k materials include hafnium silicate, hafniumoxide, zirconium oxide, aluminum oxide, tantalum pentoxide, hafniumdioxide-alumina (HfO₂—Al₂O₃) alloy, or combinations thereof. The firstcontrol gate 120 may be formed using typical CMOS processes such as,photolithography; ion implantation; diffusion; deposition includingphysical vapor deposition (PVD), metal evaporation or sputtering,chemical vapor deposition (CVD), plasma-enhanced chemical vapordeposition (PECVD), atmospheric pressure chemical vapor deposition(APCVD), low-pressure CVD (LPCVD), high density plasma CVD (HDPCVD),atomic layer deposition (ALD), spin on coating; etching including wetetching, dry etching, and plasma etching; and/or other suitable CMOSprocesses.

The substrate 110 further includes a buried oxide (BOX) layer 131 formedby a process such as separation by implanted oxygen (SIMOX), and/orother suitable processes. An opening 137 is formed at the second side113 of the substrate 110. The opening 137 may include a trench formed inone or more layers disposed on the second side 113 of the substrate 110that includes the first control gate 120. The opening 137 expose aregion underlying the first control gate 120 and body structure (e.g.,adjacent the channel region 119 of the first control gate 120). In anembodiment, the opening 137 exposes an active region (e.g., siliconactive region) underlying the first control gate 120 and active/channelregion 119 of the substrate 110. The opening 137 may be formed usingsuitable photolithography processes to provide a pattern on thesubstrate and etching process to remove materials from the buried oxidelayer 131 until the second side 113 of the substrate 110 is exposed. Theetching processes include wet etch, dry etch, plasma etch and/or othersuitable processes.

A sensing film 133 is formed conformingly to the BOX 131 and the opening137. The sensing film 133 is deposited over the sidewalls and bottom ofopening 137 and the exposed active region underlying the first controlgate 120. The sensing film 133 is compatible to biomolecules orbio-entities binding. For example, the sensing film 133 may provide abinding interface for biomolecules or bio-entities. The sensing film 133may include a dielectric material, a conductive material, and/or othersuitable material for holding a receptor. Exemplary sensing materialsinclude high-k dielectric films, metals, metal oxides, dielectrics,and/or other suitable materials. As a further example, exemplary sensingmaterials include HfO₂, Ta₂O₅, Pt, Au, W, Ti, Al, Cu, oxides of suchmetals, SiO₂, Si₃N₄, Al₂O₃, TiO₂, TiN, SnO, SnO₂, SrTiO₃, ZrO₂, La₂O₃;and/or other suitable materials. The sensing film 133 may be formedusing CMOS processes such as, for example, physical vapor deposition(PVD) (sputtering), chemical vapor deposition (CVD), plasma-enhancedchemical vapor deposition (PECVD), atmospheric pressure chemical vapordeposition (APCVD), low-pressure CVD (LPCVD), high density plasma CVD(HDPCVD), or atomic layer deposition (ALD). In some embodiments, thesensing film 133 may include a plurality of layers. A receptor such asan enzyme, antibody, ligand, peptide, nucleotide, cell of an organ,organism, or piece of tissue is placed on the sensing film 133 fordetection of a target biomolecule.

A reference electrode 139 is placed in the analyte solution 135 at thesecond side 113 of the substrate 110, functioning as the second controlgate 130. In some embodiments, the sensing film 133 is exposed to theanalyte solution 135, and the reference electrode 139 is immersed in theanalyte solution such that the second control gate 130 is a fluidicgate. The second control gate 130 is in Off-state. The analyte solutionmay be seen as a SOI transistor bulk substrate. That is, the fluidicgate 130 is turned off, while the standard MOS gate 120 functions as inOn-state. The surface potential change of the second control gate 130modulates the threshold voltage (V_(TH)) of the first control gate 120transistor through capacitive coupling. When the gate of the sensor 100(e.g., the second control gate 130) is triggered by the presence ofbio-molecule, the sensor 100 will transfer electrons and induce thefield effect charging of the first control gate 120, thereby modulatingthe current (e.g., Ids). The change of the current or threshold voltage(V_(TH)) can serve to indicate detection of the relevant biomolecules orbio-entities. Thus, the time drift effect caused by solution charging orlarge vertical electrical field is greatly reduced as the second controlgate 130 is in Off-state. A voltage biasing between the source region115, 117 and the second control gate 130 is smaller than a thresholdvoltage of the second control gate 130. More specifically, the thresholdvoltage of the second control gate 130 is approximately 0.5 V. Inconventional dual gate BioFET system, the turn-on voltage of the fluidicgate transistor is much higher than that of the standard MOSFET.Furthermore, because no voltage is applied through the second controlgate 130, the required overall voltage remains much lower than aconventional dual gate BioFET. However, because of substrate effect, thethreshold voltage of the fluidic gate still exists in trace.

Please refer to FIG. 2A. BioFET sensor 200 is nearly identical to thesensor 100. The first control gate is designated as the bottom gate(V_(BG)) 220, and the second control gate is designated as the frontgate (V_(FG)) 230 in FIG. 2A. In some embodiments, the source/drainregions contain n-type dopant. The channel region 237 is sandwichedbetween the front gate 230 and the bottom gate 220. In sensor 100, thesensing film 133 is formed on the exposed BOX 131 and the opening 137.In sensor 200, the sensing film 233 is deposited over the entire BOX 131and undergoes photoresist pattern. The portion over the channel region237 of the sensing film 233 is protected. Unprotected portions of thesensing film 233 is removed in an etch process. The etch process mayinvolve any known etch process including plasma etch, since the portionsusceptible to PID is protected. FIG. 2A shows a sensing film 233remaining on the respective surface. In FIG. 2A, sensing film 233 isshown only at the bottom surface of opening 137. However, in someembodiments the sidewalls of the opening 137 may also be covered withsensing film 233. The sensing film 233 completely covers the channelregion 237 and partially covers the source and drain region 115, 117.The partial coverage of the source and drain region may be adjustedbased on the FET design and area requirements for the sensing film 233.In order to prevent unspecified binding of biomolecules on surface otherthe sensing film 233, a blocking layer or a passivation layer may bedeposited. A passivation layer may be silicon nitride, silicon oxide, orother solid-state dielectric layers. A blocking agent, which may besolid or liquid on which a bio-molecule cannot bind or has low affinity,may be used in forming passivation layer. One example ishexamethyldisiloxane (HMDS). In another example, a protein such as aBovine Serum Albumin (BSA) is used as the blocking agent. The blockinglayer/passivation layer may be thicker or thinner than the sensing film233. In some embodiments, the molecule of interest is proton (H⁺). Whenprotons are received by the receptor on the sensing film 233, theion-dependent surface potential of the front gate 230 change. The sensor200 will transfer electrons and induce the field effect charging of thedevice, thereby modulating the threshold voltage of the bottom gate 220through capacitive coupling.

As shown in FIG. 2B, a simplified coupling circuitry is depicted. VFGrepresents the front gate voltage, VBG represents the bottom gatevoltage. In between the front and bottom gates, the capacitive couplinggoes through the gate oxide (sensing film 233) of the front gate (COX,FG) and crosses the channel region 237 of the substrate 110 (CSi), andbefore reaching the bottom gate 220, the gate dielectric layer 121 hasto be passed. The capacitive coupling principle can be deduced throughthe following equations:

$V_{{TH} \cdot {FG}} = {E_{ref} - \varphi_{s} + \chi_{sol} - \frac{\varphi_{m}}{q} + V_{{TH} \cdot {MOS}}}$${\Delta \; V_{{TH} \cdot {BG}}} = {{{{- \frac{C_{{OX} \cdot {FG}}}{C_{{OX} \cdot {BG}}}} \cdot \frac{C_{Si}}{C_{Si} + C_{{OX} \cdot {BG}}} \cdot \Delta}\; V_{{TH} \cdot {FG}}} = {{- \frac{C_{{OX} \cdot {FG}}}{C_{{OX} \cdot {BG}}}} \cdot \frac{C_{Si}}{C_{Si} + C_{{OX} \cdot {BG}}} \cdot {\Delta\varphi}_{s}}}$

V_(TH,FG) represents the threshold voltage of the front gate 230,E_(ref) represents the reference electrode potential, φ_(s) representssurface potential related to pH, χ_(sol) is surface dipole potential ofthe solution, the φ_(m)/q comes from semiconductor electron workfunction, and V_(TH), MOS represents the threshold voltage of the frontgate 230 when it acts as a standard MOSFET device.

FIG. 2C is another schematic view of the sensor 200 circuit layout. Uponreceiving the biomolecules, the surface potential of the sensing film233 changes, and through capacitive coupling, the bottom gate (V_(BG))(e.g., MOS gate) response to the change in the current. D and Srepresent drain and source regions 115, 117 respectively.

The pH value in the sensor 100, 200 has a decided effect to the accuracyof the device. The sensor has dual control gates, but the second controlgate is in Off-state, and the first control gate is in On-state. Thissystem allows less threshold voltage interference from the secondcontrol gate, which is a fluidic gate usually having larger voltagebias. The circuitry design is simpler without additional circuitry forcalibration purpose. Please refer to FIGS. 3A and 3B. FIGS. 3A and 3Bshow the pH effect to the device voltage. FIG. 3A shows the change ofthe current (e.g., I_(DS)) under different pH conditions, for example,pH 4, 6, 7, 8 and 10. The pH current sensitivity changes in acidicanalyte solution or alkali analyte solution. Threshold voltage isheavily influenced by pH variation and hence the change of current(I_(DS)).

Attention is now invited to FIG. 3B. Line 310 shows the transconductanceof the first control gate (e.g., back gate), and line 320 shows the pHsensitivity, which is derived from change of current over pH value(ΔI_(DS)/pH). The current sensitivity is optimised when the transistortransconductance is in peak. More specifically, when the first controlgate has a transconductance approximately 90 μA/V, the currentsensitivity reaches approximately 0.25 μA/pH. It suggests anoptimisation of the current sensitivity in this dual gate BioFET systemwhere the second control gate (e.g., fluidic gate) is in Off-state.

Attention is now invited to FIG. 4. FIG. 4 is a graph showing change ofcurrent against time in second of the first control gate (e.g., MOSgate) at different pH conditions. Line 410 represents the change ofcurrent (I_(DS)) at pH 4, line 420 represents the change of current atpH 7, and line 430 represents the change of current at pH 10. The linearequation indicates the slope of the drift rate in each case. Pleaserefer to Table 1.

TABLE 1 pH 4 7 10 Average Current 12.9441E−6  11.9125E−6   11.0429E−6 Sensitivity (μA/pH) 0.344 0.290 0.290 Drift Rate (μA/s) −4.00E−5 1.00E−5−1.00E−5 Drift Rate (pH/s) −1.16E−4 2.91E−5 −2.91E−5

According to FIG. 4 in conjunction with Table 1, the drift rate islevel, nearly constant along the time course. Directional drift, eitherpositive or negative cannot be observed under different pH value. Incomparison with conventional single-gate BioFET sensing system, thedrift rate reduction shows a reduction ranging from 20 (at pH 4) to 50folds (at pH 7) in this dual gate BioFET system. The drift effect isgreatly reduced due to the withdrawal of current from the second controlgate (e.g., fluidic gate).

A readout interface is designed for the dual gate BioFET. Conventionalbiosensors have, for example, single-gate FET using constant-voltageconstant-current (CVCC) structure to extract threshold variation(ΔV_(TH)) of the BioFET. In this configuration, a large circuitry isrequired with at least 2 operational amplifiers (OP AMP), 1 resistor and2 current sources. The body effect has great impact on the currentsource drifting, and therefore, due to the size and accuracy it is notsuitable in sensory array. Another example involves a differential pairof ISFET/MOSFET with indirect voltage feedback loop to MOSFET to extractthreshold voltage variation of the BioFET (ΔV_(TH,BIO)). TheDrain/source voltage varies according to the bio-signals from the ISFET,and the current source also suffers from body effect. The voltagereadout depends on two sets of FETs, and therefore, deviation adds on tothe result. Still another example of conventional readout interfaceemploys simpler circuitry with 1 operational amplifier and 1 resistorand direct voltage feedback to the reference electrode in solution toextract signals. Although body effect may reduce in this configuration,the output voltage is connected to the reference electrode in thesolution, and therefore, the direct voltage feedback can only be usedfor a single one sensor. This configuration has constant drain currentand drain voltage but is not suitable in a sensor array because ofstructural hindrance.

The BioFET sensor 100, 200 may be implemented in a readout interface ofa sensor array, and from the series of BioFET, the threshold voltage maybe efficiently collected, and at the same time sensitivity is notcompromised. BioFET sensor 100, 200 may be replaced by, for example, asingle gate BioFET having FET counterparts. It should be noted that allthe drain terminals of the FETs are connected together, and all thesource terminals thereof are connected together. Attention is nowinvited to FIG. 5, illustrating a simplified schematic diagram of BioFETcircuitry in accordance with some embodiments of the instant disclosure.V_(BG) represents the first control gate (e.g., back gate), V_(FG)represents the second control gate (e.g., front gate), D represents thedrain, and S represents the source. A reference current I_(REF) isconnected to the drain D. The reference current may be replaced by aresistor between the drain and a constant voltage source (e.g., V_(DD)).An operational amplifier is arranged in the configuration to lock thedrain voltage. The operational amplifier (i.e., feedback amplifier)includes a first input terminal, a second input terminal and an outputterminal. The first input terminal is connected to the drain terminal Dof the BioFET, and the second input terminal is connected to thereference voltage V_(D). The output terminal is connected to one of thecontrol gate that is not a fluidic gate (e.g., first control gate). Thereadout interface also includes a constant input terminal connected tothe drain terminal. Upon operation, a constant current is supplied tothe constant input terminal as a constant reference source.

In some of the embodiments, the second control gate is in On-state andthe first control gate is in Off-state. When the sensing film of theBioFET receives molecule of interest, a surface potential change isinitialised on the sensing film of the second control gate. Throughcapacitance coupling, the voltage change at the first control gate,which is at Off-state, will induce coupling effect to the second controlgate. The variation of threshold voltage (ΔV_(TH) (pH)) occurs at thesecond control gate is affected by the pH value. Also, the voltagechange of the first control gate (ΔV_(BG)) results in a variation ofthreshold voltage ΔV_(TH) (V_(BG)) at the second control gate as well.The ΔV_(TH) of the second control gate by the pH value is thereforecancelled out by the ΔV_(TH) caused by the first control gates due tocoupling effect. As a result, the ΔV_(OUT), which is equal to ΔV_(BG),is larger than ΔV_(TH) (pH), resulting in an amplification gain largerthan 1. The thickness of the oxide layer has an influence on thecoupling effect because, the oxide capacitance shown in FIG. 2B, ishighly depend on the thickness of the oxide layer. It should be notedthat the circuitry shown in FIG. 5 may be employed to a dual MOSFETstructure or an ISFET along with a MOSFET.

FIG. 6 shows an implementation of the BioFET in a sensor array.Individual threshold voltage goes through mismatch calibration beforeperforming standard sensing procedure. In the calibration mode, thesampling loop is on, while the cancel mismatch loop is off. The data ofinitial threshold voltage mismatch of each pixel is then stored in athreshold voltage storage unit. The sensor array includes a plurality ofsensor units, and the mismatch compensation process goes through each ofthe sensor units for a collective result. Therefore, in the mismatchcalibration process, a switching between each of the sensor units occurssuch that all the mismatch data from the sensor units are collected.More specifically, as shown in FIG. 6, a sensor array may include morethan one sensor unit. The mismatch calibration goes through 1-n of thesensor units, and the system switches from Sel<1>, Sel<2> . . . toSel<n> so as to collect all the mismatch data. Detail mechanism of thecalibration process is elaborated in FIGS. 7A and 7B. In the sensingmode, the sampling loop is off, while the cancel mismatch loop is on,and normal sensing operation is performed.

Attention is now invited to FIG. 7A. FIG. 7A shows a schematic view ofthe analogue design of the sampling loop and the cancel mismatch loop inaccordance with some embodiments of the instant disclosure. When thesensor undergoes mismatch calibration, a first signal (voltage orcurrent) goes through the sampling loop. That is, the first signal goesthrough the Cal. Next, a mismatch of each of the sensor unit in thesensor array is estimated and stored. The mismatch data is generatedaccording to the first signal from the sampling loop. Subsequently, amismatch compensation of each of the sensor unit is performed, and asecond signal goes through the cancel mismatch loop. As a result, theinitial threshold voltage mismatch of each sensor unit in the sensorarray is corrected. FIG. 7B shows a digital design of the sampling loopand the cancel mismatch loop in accordance with some embodiments of theinstant disclosure. When the mismatch calibration takes place, a signalgoes through the Cal path, where an analogue to digital converter ispresent and the threshold voltage mismatch is stored in the memorythrough digital interface. When the sensor is under sensing mode, asignal goes through the other path, where a digital to analogueconverter is encountered and the data is output after it is processedaccording to the threshold voltage data stored in the memory.

The instant disclosure utilizes dual gate structure and allows thecapacitive coupling effect takes place. One of the gate is in Off-state,and therefore the solution biasing voltage is reduced, and the timedrifting effect is minimized. The detection resolution of the device isenhanced because more variation is removed or attenuated from thestructural design. When implementing the structure to a readoutinterface, the amplification gain may be greater than 1. FIG. 8 showsthe process of the calibration in the sensor array, where each sensorincludes two gates. At operation 810, a first signal is produced andgoes through a sampling loop. The first signal may be a current or avoltage. At operation 830, a mismatch of each of the sensor unit isestimated and stored according to the first signal from the samplingloop. In a sensor array, mismatch data of each and every sensor unit arecollected. The mismatch data are stored in the corresponding storageunit in each sensor unit. At operation 850, a mismatch compensation ofeach sensor unit is performed, and a second signal is produced through acancel mismatch loop so as to calibrate the sensor array.

In one aspect of the instant disclosure, a biologically sensitive fieldeffect transistor includes a substrate, a first control gate and asecond control gate. The substrate has a first side and a second sideopposite to the first side, a source region and a drain region. Thefirst control gate is disposed on the first side of the substrate. Thesecond control gate is disposed on the second side of the substrate. Thesecond control gate includes a sensing film disposed on the second sideof the substrate. A voltage biasing between the source region and thesecond control gate is smaller than a threshold voltage of the secondcontrol gate.

In another aspect of the instant disclosure a dual gate field effecttransistor readout interface includes a field effect transistorincluding at least two gate terminals, a drain terminal and a sourceterminal. The readout interface further includes a feedback amplifiercomprising a first input terminal connected to the drain terminal, asecond input terminal biased at a reference voltage and an outputterminal connected to one of the control gate.

In still another aspect of the instant disclosure a method includesproducing a first signal through a sampling loop, estimating and storinga mismatch of each unit based on the first signal from the samplingloop, and performing mismatch compensation and produce a second signalthrough a cancel mismatch loop.

The foregoing outlines features of several embodiments so that thoseskilled in the art may better understand the aspects of the presentdisclosure. Those skilled in the art should appreciate that they mayreadily use the present disclosure as a basis for designing or modifyingother processes and structures for carrying out the same purposes and/orachieving the same advantages of the embodiments introduced herein.Those skilled in the art should also realize that such equivalentconstructions do not depart from the spirit and scope of the presentdisclosure, and that they may make various changes, substitutions, andalterations herein.

What is claimed is:
 1. A sensing system, comprising: a biologicallysensitive field effect transistor (BioFET) comprising: a substratehaving a first side and a second side opposite to the first side, afirst control gate disposed on the first side of the substrate, and asecond control gate disposed on the second side of the substrate, thesecond control gate including a sensing film disposed on the second sideof the substrate; a sampling circuit coupled to the BioFET, wherein thesampling circuit is configured to estimate a difference between a firstthreshold voltage of the first control gate and a second thresholdvoltage of the second control gate; and a storage unit coupled to theBioFET, wherein the storage unit is configured to store the differencebetween the first and second threshold voltages.
 2. The sensing systemof claim 1, wherein the storage unit is coupled to the first controlgate.
 3. The sensing system of claim 1, wherein the sampling circuitcomprises an analog-to-digital convertor.
 4. The sensing system of claim1, wherein the sampling circuit is configured to receive a first voltageor current signal and to estimate the difference based on the firstvoltage or current signal.
 5. The sensing system of claim 1, furthercomprising a compensation circuit coupled to the BioFET, wherein thecompensation circuit is configured to compensate for the differencebetween the first and second threshold voltages.
 6. The sensing systemof claim 5, wherein the compensation circuit comprises adigital-to-analog convertor.
 7. The sensing system of claim 5, whereinthe sampling circuit and the compensation circuit are configured to beturned on sequentially.
 8. The sensing system of claim 1, furthercomprising a readout interface coupled to the BioFET, wherein thereadout interface comprises an operational amplifier.
 9. The sensingsystem of claim 1, wherein the substrate comprises a source regionshared by the first and second control gates; and wherein an appliedbias voltage between the source region and the second control gate issmaller than the second threshold voltage.
 10. A sensing system,comprising: an array of biologically sensitive field effect transistors(BioFETs), wherein each BioFET of the array of BioFETs comprises: asubstrate having a first side and a second side opposite to the firstside, a first control gate disposed on the first side of the substrate,a buried oxide layer disposed on the second side of the substrate,wherein an opening is formed in the buried oxide layer to expose thesecond side of the substrate, and a second control gate disposed on thesecond side of the substrate, the second control gate including asensing film disposed on the second side of the substrate; an array ofsampling circuits, wherein each sampling circuit is coupled to acorresponding BioFET in the array of BioFETs and is configured toestimate a difference between a first threshold voltage of the firstcontrol gate and a second threshold voltage of the second control gateof the corresponding BioFET; and an array of storage units, wherein eachstorage unit is coupled to the corresponding BioFET in the array ofBioFETs and is configured to store the difference between the first andsecond threshold voltages of the corresponding BioFET.
 11. The sensingsystem of claim 10, further comprising an array of switching circuits,wherein each switching circuit is coupled to the corresponding BioFET inthe array of BioFETs and wherein the array of switching circuits isconfigured to sequentially switch on the corresponding BioFETs toestimate the difference between the first and second threshold voltagesof the corresponding BioFETs.
 12. The sensing system of claim 10,wherein each sampling circuit comprises an analog to digital convertor.13. The sensing system of claim 10, wherein each sampling circuit isconfigured to receive a first voltage or current signal and to estimatethe difference based on the first voltage or current signal.
 14. Thesensing system of claim 10, further comprising an array of compensationcircuits, wherein each compensation circuit is coupled to thecorresponding BioFET in the array of BioFETs and is configured tocompensate for the difference between the first and second thresholdvoltages of the corresponding BioFET.
 15. The sensing system of claim14, wherein each compensation circuit comprises a digital-to-analogconvertor.
 16. The sensing system of claim 10, further comprising areadout interface coupled to the array of BioFETs, wherein the readoutinterface comprises an operational amplifier.
 17. A method of thresholdvoltage mismatch calibration for a sensing system that has an array ofdual gate transistors, comprising: providing a first voltage or currentsignal through a sampling circuit coupled to a dual gate transistor inthe array of dual gate transistors; estimating, with the samplingcircuit, a threshold voltage mismatch between threshold voltages of thegates of the dual gate transistor based on the first voltage or currentsignal; storing the threshold voltage mismatch of the dual gatetransistor in a storage unit; and compensating the dual gate transistorfor the threshold voltage mismatch based on the stored threshold voltagemismatch.
 18. The method of claim 17, further comprising switchingbetween dual gate transistors in the array of dual gate transistorsafter performing the providing, the estimating, the storing, and thecompensating for each of the dual gate transistors.
 19. The method ofclaim 17, wherein the storing comprises storing the threshold voltagemismatch through a digital interface.
 20. The method of claim 17,further comprising maintaining one of the dual gates of the dual gatetransistor in an off-state.